Assessment of Driving Impairment from Cannabis

Stephen Schmitz, PhD, MAForensic NeuropsychologistDirector, The Brain and Behavior Clinic - Denver and BoulderClinical and Scientific Advisor, DriveABLEsps@bbcneuro.com

303.938.9244

National Marijuana Laws

46 states have medical MJ lawsMedical MJ laws vary

30 states and DC have laws in some form broadly legalizing MJ

8 states and DC have laws legalizing recreational MJ

Federal law classifies MJ as a Schedule 1 drug (CSA)MJ dangerous, highly addictive, and having no

medical value Inherent conflict between state and federal law

Colorado Legalization of Marijuana

1975 – Marijuana decriminalized in Colorado November 2000 – Amendment 20: First medical

marijuana law November 2012 – Amendment 64: Ended

marijuana prohibition May 2013 – DWDI 5ng/ml permissible inference

standard – but defense can argue not impaired January 2014 – Full legalization statewide October 2017 – Colorado ranked #1 in the nation

for adult MJ use

Impact of Decriminalization of Marijuana on Driving Fatalities in Colorado

MVA Fatality – Driver positive for marijuana# of deaths

2013

55

2016

125

MVA Fatality –Marijuana related# of deaths

2009 – 2012(Pre-Legalization Era)

53

2013 – 2016 (Legalization Era)

88(66% increase)

MVA Fatality – Driver positive for marijuana –Percent of all traffic deaths

2009 and prior

9%

2016 and since

21%

Prevalence of MJ Availability

McDonald’s 208

Starbucks 392

Marijuana Retail Stores 491

Marijuana and Driving Ability

MJ most frequently detected drug (except ETOH) in crash-involved drivers

Effect on CNS functions necessary for safe drivingMemory Sustained and divided attentionReaction time TrackingMotor functioning

Association not causation

Marijuana and Increased Crash Risk

YES Systematic reviews and meta-analyses of epidemiological

studies2x increased risk of a motor vehicle collision

Asbridge, 2012; Li, 2012; Hartman and Huestis, 2013NO No increase in crash risk after adjusting for alcohol and

demographicsRomano, 2013; Elvik, 2013DRUID study

9 European countries – seriously injured and fatality crashes

1.33 – 1.39x increased risk – NOT statistically significant

Drug and Alcohol Crash Risk: A Case-Control StudyUS Department of Transportation 2015

National Highway Traffic Safety AdministrationCase-control methodology3000 crash-involved drivers – 6000 control subjects selected

for each crash driver66% property damage only 33% injury crash 1% fatality crashOral fluid or Blood draw

Unadjusted and Adjusted Odds Ratios for Age, Gender, and Race

Unadjusted odds ratio significantly associated with THC (1.25x)

Adjusted odds ratio not significantly associated with THC (1.05x)

Current Colorado Marijuana Driving Law

5ng/ml permissible inferenceDriver can argue not impaired while driving

Too low or too high? Too low

Heavy users develop tolerance for impairing effects

No scientific basis for a 5ng/ml THC legal limit impairing driving ability

Too highAny MJ impairs cognitive functioningEssentially establishes a license to drive stonedNo scientific basis for a 5ng/ml THC legal limit

impairing driving ability

Meta-analysis of cognitive effects of smoked cannabis,comparing dose, plasma THC levels, and test performance

Following a single THC exposure to occasional users, a whole blood THC of 1.9 ng/ml corresponded to a blood alcohol concentration of 0.05%*

* Based on 888 neuropsychological effects reported in 78 studies employing THC doses of 1 - 52 mg in occasional users.The range of blood THC associated with ± 10% variation in this level of impairment was 1.7 to 2.3 ng/ml.

After 4.75 hours <15% of the tests results were impaired, a performance found at BAC < 0.03%

[Berghaus, G, Sticht G, Grellner W et al. Meta-analysis of empirical studies concerning the effects of medicines and illegal drugs including pharmacokinetics on safe driving." Bergisch Gladbach: BASt2010. Report No.: D 1 (2011)]

Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users[Ramaekers J et al. J Psychopharm 23:266-277; 2009]

•12 occasional cannabis users and 12 heavy users participated in double-blind, placebo-controlled, 2-way balanced trial.

• Endpoints included critical tracking task, and divided attention tasks• Paced smoking of placebo or joint (13% THC) delivering 500 μg/kg dose in 10 minutes (≈25 hits)• Whole blood THC 15 min after smoking:

23.7 ± 14.1 ng/ml (heavy users); 10.4 ± 4.6 ng/ml (occ users)

critical tracking test (standardized score)

Heavy users were tolerant to impaired performance after THC

Occ. users + THC

divided attention task

Occ. users + THCOcc. users + THC

Psychomotor and neurocognitive effects in occasional and frequent smokers

Both groups feel “high”Frequent users tolerant to slowed reaction time [Desrosiers N et al. J Anal Toxicol 39:251-261; 2015]

[Hart C et al. Pharmacol Biochem Behav 96:333-341; 2010]

Neurophysiological and cognitive effects of smoked marijuana in frequent users

Hart et al, 2011

In an on-the-road driving test, oral dronabinol (THC 20 mg) significantly impaired road tracking (SDLP) and car following performance in occasional but not heavy cannabis users

Blood THC at 1.5 hr post 20 mg5.1 ± 1.1 ng/ml (heavy users)3.1 ± 0.7 ng/ml (occ. users)

dotted line equates to BAC 0.05%

Bosker W et al. Addiction 107:1837-1844; 2012

Blood THC Levels Decline Rapidly

Tolerance in Chronic Users

Days of supervised abstinence (subject L)

Karschner et al. Jour Annal Toxicol. 33: 469 – 477, 2009

Observational Study of Driving Impairment in Occasional Versus Heavy Marijuana Users

Co-PI’s: Michael Kosnett & Ashley Brooks-Russell - CU Anschutz

Co-investigators: Tim Brown & Gary Milavetz - U of Iowa Chris Halsor, Dave Carbonetti - Understanding Legal

Marijuana Greg Dooley – CSU Stephen Schmitz - DriveABLE and Private Practice Sam Wang, CU Anschutz Becki Bartelson,Victoria Anderson, AR Olson, Kyle

Friedman - Denver Health

Primary Aim

Compare driving impairment in occasional vs. heavy marijuana users, before and after smoked marijuanaDriving simulator Standardized Field Sobriety Test iPad-based neurocognitive test battery

Secondary Aims

Calculate the sensitivity, specificity and predictive value of the iPad CARE test battery for validated benchmarks of driving impairment measured in the MiniSim.

Determine if blood cannabinoid profiles predict driving impairment differentially in occasional and heavy (i.e. daily) marijuana users as measured on the three driving assessment tools.

Evaluate the predictive value of a blood THC concentration of ≥ 5 ng/ml (and other blood THC cut-points, including various metabolite ratios) for driving impairment in occasional marijuana users and in heavy marijuana users.

Pre-Post Change Analysis

3 groups – 30 ss each Occasional users

MJ use ≥ 1 day/week and ≤ 2 days/week (last 30 days)

Heavy users≥ daily (last 30 days)

Non-usersNo MJ use (last 30 days) ≤ 2 times/month (last 90 days)

Baseline assessments

(after overnight abstinence)

Smoking session

Post assessments

Methods

Pre-screening Inclusion/exclusion criteria

Screening visitUrineBreathalyzerDriving simulator

7 minutesSimulator adaptation syndrome

Visual acuity Study diary

MJ use, medications, alcohol, sleep duration2 days before first study visit

National Advanced Driving Simulator – MiniSim

Simulated Scenarios

Highway and city driving environmentsCollision situation Following Lane positionDistractor

Each subject will undergo 2 sessions Duration – 30 minutes

Braking Lead Vehicle Braking While the driver is distracted, the lead vehicle which is 3.5seconds ahead brakes to 20 mph at a high level of deceleration (0.85g) (~2.25s), and then maintains 20 mph for 5 seconds. Oncoming traffic prevents passing.

Braking Lead Vehicle Stopped While the driver is distracted, the lead vehicle which is 4 seconds ahead brakes to a stop at very high level of deceleration (2g)

Steering Curve Departure Driver going around a tightening radius curve at too great a speed (missing reduced speed sign) requiring a steering response

Steering Slick Road Departure Similar to Curve Departure but simulates loss of control due to weather conditions as opposed to aggressive driving.

Steering Avoidance Departure - right incursion Driver traveling on a two-lane roadway. Vehicle enters roadway from hidden driveway requiring steering response

Steering Wind Gust Driver traveling on two-lane roadway. Wind gust from the left pushes the driver requiring a steering response for recovery.

Steering Obstacle Avoidance Driver traveling on a multilane roadway. Desk falls out of the back of truck requiring driver to make steering response

Steering Left Incursion Driver traveling on a two-lane roadway. Oncoming vehicle crosses into driver's lane requiring a steering resposne.

Braking Lead Vehicle Braking Traveling on a two-lane roadway, while driver is distracted, vehicle slows to turn onto interstate causing lead vehicle to brake

Varied Red Light Runner Driver approaches signalized intersection with the green light. Hidden vehicle from the left runs the red light

Varied Left Turn Across Path Driver approaches intersection to turn left. Oncoming traffic is hidden. As driver accelerates oncoming traffic enters the intersection

Braking Lead Vehicle Revealed Following a vehicle at 40 mph with a time headway of 2.25 seconds, the lead vehicle changes lanes while the driver is engaged in a distraction task revealing a stopped lead vehicle.

MiniSim - Limitations

Not highly correlated with actual driving More relaxed and less “controlled” in a simulator Sd larger

Simulator adaptation syndrome

Standardized Field Sobriety Test -SFST

Horizontal Gaze NystagmusVisually focus on object moved horizontally and

vertically Walk and Turn

9 heel-to-toe steps forward and back along straight line

One Leg Stand Stand on one leg with other leg stretched out in

front of themCount out loud for 30 seconds

Sensitive test related to BAC Sensitive-ish to marijuana

Sensitivity of SFST to Detect Impairment Due to Marijuana Intoxication

40 Ss Occasional users Placebo or marijuana Low dose - 1.74% THC High dose – 2.93% THC One cigarette fully consumed Blood sample

Prior, immediately after smoking, and every 20 min for 2 hrs

SFST5 min after smoking, 55 min, 105 min

Papafotiou et al. PsyPharm, 2005, 180, 107 - 114

SFST and Marijuana

5 minutes 55 minutes 105 minutes

Impairment on SFST in Low (1.8%) vs High (3.0%) THC Content Levels

Stough, et al. 2006, NDLERF

DriveABLE Ipad - Cognitive Ability Real-Time Evaluation (CARE)

Originally developed driving assessment tools for dementia/TBIOn-Road evaluationPC based evaluationOver 100,000 evaluationsPredictive values > .88

Roadside assessment tool in development - CARE Ipad based Measure of real-time cognitive abilities correlated

with driving 5-10 minute administration

Cognitive Ability Real-Time Evaluation (CARE)

Evidence based Correlates to actual behind the wheel driving riskPurposely focused on ease of useQuick to administer Legally defensible in court

Task 1: Motor Speed & Control

Task 2: Span of Attentional Field

Task 3: Spatial Judgement & Decision

Task 4: Attentional Shifting

Task 6: Identification of Driving Situations

Task 5: Memory & Exective Function

Task 1: Reactions

Task 2: Judgement

Task 4: Memory Function

Task 4: Control

DriveABLE Cognitive Assessment Tool Cognitive Ability Real-Time Evaluation

Cognitive Ability Real-Time Evaluation (CARE)

Challenges

Observational study (IRB) University legal concerns Finding off-campus space Timeline

Begin recruitment: early 2018 Initiate study: early 2018 – mid 2019 Share findings: late 2019 – early 2020

Summary of Key Points

Use of THC can result in acute CNS effects that may impact cognitive performance and driving in some users for several hours

Tolerance to CNS effects that mitigates impairment may develop in chronic frequent users

Blood tests that measure THC and other cannabinoids in blood may correlate with impairment in some users (moreso occasional users than chronic users)

Additional research is needed regarding the temporal pattern of pharmacokinetic and pharmacodynamic effects, including the utility and predictive value of “roadside measurements”